A systematic investigation of the kinetics of rapid axonal transport is proposed. Efforts will be made to answer three main questions: 1) What are the limits to the concentration of material that can be transported along an axon? 2) Are these limits determined by the number of axonal microtubules? 3) Is transport velocity a function of the concentration of material actually being transported? The transport of the adrenergic enzyme dopamine-Beta-hydroxylase and of proteins labeled by incorporation of 3H-leucine in rabbit peroneal and frog sciatic nerve will be measured. Nerves will be subjected to various small step-gradients of temperature in vitro in order to produce local increases or decreases in the concentration of transport overloaded and partially unloaded nerves will be compared with the effect of the same drugs in normal nerves. Stop-flow techniques developed in this laboratory will be used to assess the effects of the experimental conditions on transport-velocity. Correlative measurements will be made of microtubular numbers and density in electron micrographs of nerves fixed after exposure to such conditions. It is anticipated that the results of this project will help define the fundamental kinetic properties of rapid axonal transport and provide a basis for developing improved models of the process.